Study calls antibiotic-asthma link into question

NEW YORK (Reuters Health) - While some studies have suggested that giving babies antibiotics might boost their risk of asthma later on, a new analysis concludes that much of that evidence is flawed.

The theory behind the proposed link is that early exposure to bacteria and other microbes trains the immune system to move into infection-fighting mode, and away from a tendency to attack harmless substances -- which is at the heart of allergic reactions and asthma.

But the new analysis, of 21 studies conducted since 2002, found that the majority had limitations that could have biased them toward finding a link between infant antibiotic use and asthma risk.

According to the researchers, several studies were hampered by "reverse causation" -- the fact that babies' wheezing symptoms could have prompted the antibiotic prescriptions, rather than antibiotics causing wheezing and asthma to develop later on.

Babies and young children commonly develop wheezing when they have a respiratory infection, so doctors may prescribe an antibiotic. But for some children, that wheezing is an early indication of asthma.

A couple of studies in the current review could not rule out the possibility of reverse causation. In a few others, there was initially a connection between early antibiotic use and asthma, but it disappeared after the researchers controlled for reverse causation.

In other studies, the issue was "confounding by indication," that is, the infection for which the antibiotic was prescribed could be the real risk factor for wheezing and asthma.

One study found babies with "chest" infections with symptoms of wheezing were twice as likely to be prescribed antibiotics as babies with upper respiratory infections, like colds. And it was the chest infections, rather than the antibiotics, that appeared to account for the increased risk of asthma symptoms before the age of five.

Several other studies did not account for the possibility of confounding by indication.

"The overall conclusion of our meta-analysis was that after excluding the studies that were at high risk of bias due to reverse causation and confounding by indication, there was only a very small increased risk of wheeze/asthma in children exposed to antibiotics in infancy," said lead researcher Dr. John Penders, of Maastricht University Medical Center in The Netherlands.

Another issue, he told Reuters Health by e-mail, is that only three of the studies looked at asthma risk beyond the age of five or six.

Asthma is tricky to diagnose in children younger than six, both because wheezing can be caused by respiratory infections rather than asthma, and because young children usually cannot perform the lung function tests used to objectively diagnose asthma.

When Penders' team combined the results of the three studies that included older children, there was no clear association between early antibiotic use and later asthma risk.

The bottom line, the researchers write in the European Respiratory Journal, is that there is still a need for more well-designed studies that follow children over a longer period.

In the meantime, though, it is important to give babies and young children antibiotics only when absolutely necessary, according to Penders.

Many respiratory infections, including the common cold, are caused by viruses and do not respond to antibiotics, which kill bacteria. And overuse and improper use of antibiotics, Penders noted, is contributing to the widespread problem of drug-resistant bacteria.

"Studies have shown that up to 50 percent of antibiotic prescriptions for children given by primary care physicians are unnecessary," Penders said, adding that the rate does vary widely among countries.

Dr. Anita Kozyrskyj, an associate professor at the University of Alberta in Edmonton, Canada, agreed on the need for further, long-range studies.

In an e-mail to Reuters Health, she pointed out that her own 2007 study, which was included in the analysis, did find a link between antibiotic prescriptions for non-respiratory conditions -- like urinary tract infections -- and later asthma risk.

Further studies that zero in on the reasons for babies' antibiotic prescriptions would be helpful, according to Kozyrskyj.

She also agreed on the need for "judicious" use of antibiotics in infants -- especially when it comes to so-called broad-spectrum antibiotics, which target a wide range of bacteria.

What is "worrisome," Kozyrskyj said, is that guidelines in both the U.S. and Canada now call for greater use of wide-spectrum antibiotics for kids' ear infections.

"In Sweden and Norway, basic penicillin remains the antibiotic of choice," she noted.

Middle-ear infections are among the most common reasons for antibiotic prescriptions in American toddlers. But about 80 percent of children would get better without antibiotics, according to the American Academy of Pediatrics.

In its treatment guidelines, the academy says infants and children without severe symptoms can often wait 48 to 72 hours before starting antibiotics to see if the infection improves on its own.